The primary emphasis of this proposal is to study genes and gene products necessary for the morphogenesis of the central nervous system, specifically the forebrain. The holoprosencephaly (HPE) sequence is a structural anomaly characterized by abnormal midline development of the brain and face. We propose the hypothesis that gene rearrangements, e.g. translocations or deletions, alter gene expression, leading to the clinical features of the holoprosencephaly sequence. To address this hypothesis the proposed research will concentrate on one form of holoporosencephaly associated with a newly identified chromosomal t (7;9) translocation breakpoint in 7q36 and a number of deletions encompassing this breakpoint. Available cDNA libraries from early mouse embryos and human fetal brain-specific cDNA libraries will be screened with YACs from the HPE breakpoint. cDNA clones from these libraries that map to the HPE breakpoint in 7q36 are candidates for a gene necessary for normal brain development.